The effects of prostaglandin and mating on release of LH in the female rabbit

The release of LH in response to prostaglandin (PG) treatment of female rabbits in various reproductive states was compared with the surge following mating. Intracarotid infusion of PGE-2 or PGF-2alpha (0-3--900 microgram/h) into non-receptive and pseudopregnant does resulted in small, 2--4-fold elevations in jugular vein LH concentration. Similar doses of PGF-2alpha in oestrogen-pretreated, oestrous does stimulated a 13-fold increase in plasma LH levels. Mating resulted in a much larger release of LH, as plasma levels increased approximately 60-fold from 1-1 +/- 0-2 (S.E.M.) ng/ml to 67-8 +/- 10-5 ng/ml. These results indicate that PG can stimulate the hypothalamic-hypophysial axis to release LH in non-receptive, pseudopregnant and oestrogen-pretreated, oestrous rabbits.     

Norepinephrine stimulates LH-RH secretion into the hypophysial portal blood of the rat

The present study was designed to investigate the effect of intracerebroventricular infusion of norepinephrine (NE) on the secretion of luteinizing hormone-releasing hormone (LH-RH) into the hypophysial portal blood of steroid-primed ovariectomized rats. Saline infusion into the third ventricle caused no significant change in LH-RH levels. NE infusion (20 micrograms) resulted in a significant release of LH-RH (p less than 0.05) into the portal blood 10-30 min later. This endogenous LH-RH was similar to synthetic LH-RH when characterized by thin-layer chromatography. LH secretion in similarly treated rats but with intact portal vessels, also was significantly elevated (p less than 0.05) at 20 and 40 min after the start of NE infusion. These results show that NE stimulated the secretion of LH-RH into the hypophysial portal blood and this correlated with an enhanced release of LH.     

Comparison between the biological effects of LH-RH and buserelin on the induction of LH release from hemi-pituitary glands of female rats in vitro

The biological effects of LH-RH and the agonist [D-Ser(But)6-des Gly10]-LH-RH(1-9)-ethylamide (buserelin) were compared during 8 h of incubation with female rat hemi-pituitary glands. Similar dose-response relationships were found for LH-RH and buserelin as concerns the release of luteinizing hormone (LH) by pituitary glands from intact and ovariectomized rats. Also the LH secretion patterns from glands of intact rats were similar: an initial low response was followed by a fast increase (priming effect) after which the response declined again (desensitization). In a subsequent experiment pituitary glands from ovariectomized rats were first exposed to LH-RH or buserelin for 4 h and then further incubated in medium only. After discontinuation of the stimuli the rate of LH release decreased in all cases, but this decrease was significantly greater when the glands had been exposed to LH-RH. Short-term (1/2, 1 or 2 h) exposures to LH-RH or buserelin followed by an intervening period (1 1/2, 1 or 0 h, respectively) of incubation in medium only resulted in an almost similar, significant increase in the subsequent protein synthesis-independent LH response to LH-RH (priming effect). Only preincubation with LH-RH for 2 h was significantly more effective. The results demonstrate equal intrinsic activities for LH-RH and buserelin. Differences in the biopotencies for LH-RH and buserelin in vivo and in vitro may occur only after discontinuation of the external stimuli.     

Effect of prolactin on the LH response to synthetic LH-RH in ovariectomized ewes.

When ovariectomized ewes were treated with LH-RH, all 3 receiving prolactin infusion and 4 out of 5 receiving an infusion of NaCl solution responded.     

Pituitary responsiveness to synthetic LH-RH and pituitary LH content at various reproductive stages in the sheep.

In sheep the basal concentration of LH in jugular vein plasma was significantly higher during the first 50 days of gestation in late pregnancy or at parturition. The pituitary response to a single i.v. injection of 200 microng synthetic LH-RH was determined at different stages of gestation and compared with that of anoestrous and cyclic sheep. Pituitary response to LH-RH decreased progressively with advancing gestation: by 56 days after mating the response had declined to 35% and by parturition to 14% of the value in anoestrous sheep. The pituitary response to LH-RH increased after parturition and the pattern of recovery differed in non-lactating and lactating sheep. By 63 days postpartum the response to LH-RH in non-lactating and lactating animals had returned to values similar to those in sheep during anoestrus and sheep during the luteal phase of the oestrous cycle. A decrease in pituitary responsiveness during pregnancy was associated with a decrease in pituitary content of LH. The quantity of LH released in response to a standard injection of LH-RH was linearly related to pituitary LH content.     

Differences in the rabbit uterine response to progesterone as influenced by growth hormone or prolactin

The direct effect of growth hormone (GH) on the uterine response to progesterone was tested by using ovariectomized rabbits (at least 12 weeks) treated with GH; GH + progesterone; or progesterone alone. These results were compared with the effect of prolactin or prolactin + progesterone on the uterus. Prolactin treatment produced an increase (P less than 0.01) in the endometrial surface area and restored cytosolic oestrogen and progesterone receptor concentrations to oestrous control values. The sequential treatment of does with prolactin + progesterone stimulated uteroglobin production to a concentration equal to that found in intact rabbits on Day 5 of pregnancy. In contrast, GH treatment had no effect on endometrial surface area, produced an increase in the concentration of cytosolic oestrogen receptor but did not produce an increase in the concentration of progesterone receptor. The sequential treatment of does with GH + progesterone failed to stimulate uteroglobin secretion above control (progesterone alone) values. It is concluded that the action of prolactin in the rabbit uterus is no generally somatogenic; rather, prolactin increases the concentration of progesterone receptor and thereby enhances the uterine response to progesterone.     

Effect of an antagonistic analog of LH-RH on haloperidol-induced hyperprolactinemia in female rats

The effects of prolonged treatment with the antagonistic analog of LH-RH (N-Ac-D-p-Cl-Phe1,2, D-Trp3,D-Arg6,D-Ala10) LH-RH (ORG 30276) on the hyperprolactinemia induced by haloperidol were investigated in intact or ovariectomized female rats. Treatment with ORG 30276 for 20 days significantly reduced prolactin levels elevated by daily injections of haloperidol in intact as well as in ovariectomized rats. Administration of ORG 30276 also significantly decreased serum LH levels in both types of rats. It is concluded that the LH-RH antagonist ORG 30276 is able to counteract the hyperprolactinemic effect of haloperidol. This effect might be due to a blockade of the action of endogenous LH-RH on the gonadotrophs, which results in a suppressing of the paracrine action of these cells on the lactotroph.     

Pharmacological evidence that LH-RH action on lordosis behavior is mediated through a rise in cAMP

The effect of two phosphodiesterase inhibitors, theophylline (THP) and 1-methyl-3-isobutyl-xanthine (MIX), on the lordosis response induced by three dose levels (0.5, 1, and 5 μg) of LH-RH was studied in ovariectomized estrogen-primed rats (estradiol benzoate, 4 μg). Neither THP (10 mg) nor MIX (2mg) facilitated lordosis behavior in estrogen-primed rats. Combined administration of 10 mg of THP with LH-RH exerted only a slight facilitatory effect on lordosis behavior. Administration of 2 mg of MIX significantly synergized with LH-RH for the facilitation of lordosis. The results suggest that LH-RH elicits sexual behavior by increasing cAMP levels in neurons related to the expression of lordosis behavior.     

Variability in the response of the rabbit uterus to progesterone as influenced by prolactin

Ovariectomized rabbits from different breeders were treated at different times of the year with prolactin alone or with progesterone and the production of uteroglobin by the uterus was studied. There were seasonal, strain and dose variables in the uterine response to prolactin and progesterone. Treatment with prolactin (at 1 mg/day) plus progesterone generally induced higher levels of uteroglobin production than did treatment with progesterone alone. The differences were greatest in the winter for Tennessee animals and in the spring for animals from the New Mexico and North Carolina colonies. Ovariectomy produced a decrease (P less than 0.01) in the concentration of cytosolic oestrogen and progesterone receptors, and prolactin treatment restored the concentration to oestrous control values. However, there were no seasonally dependent changes in the concentration of the receptors for any of the treatment groups. Increased doses of prolactin (2 mg/day) induced high levels of uteroglobin production and new proteins to appear in uterine secretions of long-term ovariectomized rabbits but much lower levels (10-11%) when given to pregnant does. Additional ovulations were also noted plus adverse effects on the embryos.     

Presence and activity of LH-RH in the mid-term human fetus.

Immunoreactive LH-RH was present in all the hypothalamic and cortical extracts of mid-term human fetuses studied and in the cortical tissue removed from the two youngest fetuses. Gonadotrophin-releasing activity of hypothalamic and cortical extracts was demonstrated by the significant rises of circulating LH after infusion into oestrogen and progesterone-primed ovariectomized rats.     

Oestrous and ovarian activity in a female jaguar (Panthera onca).

The mean +/- s.e.m. duration of oestrus was 12.0 +/- 1.0 days (n = 7) and the oestrous cycle length was 47.2 +/- 5.4 days (n = 6) for a captive jaguar. Ovulation did not occur spontaneously, but was induced by treatment with hCG or LH-RH.     

Modifications of post-coital LH secretion and oestrous behaviour induced by drugs in ovariectomized rats.

The post-coital discharge of LH was studied in ovariectomized rats primed with steroids and injected with drugs that modify oestrous behaviour. It was found that LH release was absent in receptive rats treated with p-chlorphenylalanine which also exhibited abnormal oestrous behaviour. Rats primed with oestrogen and progesterone and injected with DL-amphetamine showed no release of LH after mating and a decreased lordotic response.     

Response of cyclic and post-partum suckled cows to injections of synthetic LH-RH.

Doses of 125, 250 or 500 micrograms LH-RH were injected i.m. into suckled beef cows on approximately Day 11 of an oestrous cycle synchronized by prostaglandin treatment. There was a positive linear relationship between dose of LH-RH and the area under the measured LH peak. Administration of 500 micrograms LH-RH as a single injection to suckled cows 13-32 days post partum resulted in LH release but failed to induce normal ovarian activity. A small transient rise in plasma progesterone for 6--9 days occurred at the expected time after injection in 50% of animals. Administration of 500 micrograms LH-RH to suckled beef cows approximately 20--30 days post partum and a second injection approximately 10 days later at the time when the resulting transient rise in plasma progesterone had returned to basal values induced normal cyclic activity (as shown by progesterone concentrations and observed oestrus) at 35 days compared with 70 days for untreated controls. Pituitary responsiveness to LH-RH, as assessed by LH levels, was found to increase up to 20 days post partum.     

Relation between circulating sex steroid concentrations and sexual behaviour during pregnancy and post partum in the domestic rabbit

Sexual behaviour of 16 female and 12 male rabbits was studied during pregnancy and early post partum. The main behavioural events of the male (nuzzling and mounting) did not differ in the presence of receptive or non-receptive females. When introduced into the cage of the male, receptive and non-receptive females flattened to the floor or circled around. Sexual receptivity to males decreased in early pregnancy and increased to a maximum a few days around parturition; on Days 1 and 6 post partum, all experimental rabbits submitted to mating. Two groups of females were distinguished: one group submitting to mating whatever the stage of pregnancy, the second being receptive only during the few days before parturition or post partum. During pregnancy and early post partum there was no relation between the colour of the vulva and the female sexual behaviour. Does remained sexually receptive even when progesterone concentrations were high. Nevertheless, the number of receptive females was higher when progesterone concentrations decreased around parturition and the mean daily progesterone values were consistently higher in non-receptive than in receptive females. Oestrogen concentrations during pregnancy were very low and were not related to receptive behaviour.     

Attenuating effects of prior oestradiol benzoate priming on 5-HT-mediated lordosis behavior in rats are dose-dependent

The present study was designed to investigate the role of the 5-HT7 receptors in lordosis and compare the lordotic responses with 5-HT1A agent under the influence of different steroid-priming regimens in ovariectomized, non-receptive and receptive rats. 8-OH DPAT, a 5-HT1A agonist and 5-CT, a 5-HT7 agonist inhibited the lordosis differently in non-receptive and receptive rats, however, the response was attenuated in a dose-dependent manner following 5-CT treatment in the first two tests. Treatment with 5-HT1A antagonist, WAY 100 135 caused a protective effect which was evident in the second test only. Priming with 25 microg OB attenuated in the first test in non-receptive rats whereas the same dose repeated a similar pattern in receptive rats. The attenuation of LQ was evident in rats treated with 5-HT7 antagonist, SB 269970-A. This finding shows that WAY 100 135, a 5-HT1A antagonist has potency to attenuate inhibitory influence of 8-OH DPAT by enhancing lordosis behavior acutely in female rats with a low estrous state. Treatment with 5-CT and SB 269970-A as 5-HT7, agonist and antagonist, respectively, have mimicked 5-HT-mediated lordotic response as moderate affinity towards 5-HT1A receptors has been reported. This offers a comparable effect on lordosis as a result of the two 5-HT agents used.     

Luteinizing hormone response to injection of synthetic gonadotrophin releasing hormone or infusion of oestradiol-17 beta in heifers

The effects of intracarotid injection of synthetic gonadotrophin releasing hormone (GnRH) as well as of intracarotid oestradiol infusion, on plasma luteinizing hormone (LH) levels in heifers were examined. The LH response in five ovariectomized heifers after administration of 100 μg of GnRH was biphasic, and more abrupt than in the cycling animals or in heifers with reproductive disorders. The first LH peak in ovariectomized heifers appeared 2 min after injection (fast response), and the second one about 15–30 min later (slow response). In all other heifers the fast response was never observed, and the mean estimated LH secretion was much lower. The LH response to intracarotid infusion of 3 μg of oestradiol-17β observed in ovariectomized heifers was also biphasic, although the first peak of LH was observed 4 h after the infusion had been terminated.     

Growth hormone response to thyrotropin-releasing hormone in liver cirrhosis: unique alteration in anterior pituitary responsiveness to hypothalamic hormones

Patients with chronic liver diseases were evaluated for: 1) the ability of somatostatin to affect the thyrotropin-releasing hormone (TRH) induced growth hormone (GH) rise; 2) the competence of luteinizing-hormone releasing hormone (LH-RH) to release GH; 3) the non-specific releasing effect of TRH and LH-RH on other anterior pituitary (AP) hormones. In 6 patients, infusion of somatostatin (100 micrograms iv bolus + 375 micrograms i.v. infusion) completely abolished the TRH (400 micrograms i.v.)-induced GH rise; in none of 12 patients, of whom 7 were GH-responders to TRH, did LH-RH (100 micrograms i.v.) cause release of GH; 4) finally, LH-RH (12 patients) did not increase plasma prolactin (PRL) and TRH (7 patients) did not evoke a non-specific release of gonadotropins. It is concluded that: 1) abnormal GH-responsiveness to TRH is the unique alteration in AP responsiveness to hypothalamic hormones present in liver cirrhosis; 2) the mechanism(s) subserving the altered GH response to TRH is different from that underlying the TRH-induced GH rise present in another pathologic state i.e. acromegaly, a condition in which the effect of TRH escapes somatostatin suppression and LH-RH evokes GH and PRL release.     

[D丙~6,脯~9乙基胺]-促黄体素释放激素LH-RHA对妊娠兔子宫内膜多聚核糖体mRNA的作用

本实验制备了非孕兔、孕兔和绐孕兔注射高剂量[D丙‘,脯’乙基胺]-促黄体素释放激素(LH-RH A)不同天数的子宫内膜多聚核糖体,并从多聚核糖体提取mRNA,在网织红细胞无细胞翻译系统中测定了活性。结果指出用LH-RH A处理后多聚核糖体mRNA量减少,其翻译活性降低,在体内实验中核糖体mRNA诱导兔子宫分秘蛋白的合成也受到抑制,特别是分子量大约为22,000和69,000左右的分泌蛋白合成受到明显抑制。     

Prolactin as a factor in the uterine response to progesterone in rabbits

The direct effect of prolactin on uteroglobin production and on uterine endometrial oestrogen and progesterone receptor concentrations was tested by using ovariectomized rabbits (at least 12 weeks) treated with prolactin; prolactin + progesterone; prolactin + oestradiol + progesterone; oestradiol + progesterone; or progesterone alone. Prolactin treatment produced a significant (P less than 0.05) increase in the concentration of cytosolic oestrogen and progesterone receptors, restoring the concentrations to values found at oestrus. However, the concentration of nuclear receptors remained low. In the remaining treatment categories there was no significant (P greater than 0.05) increase in the concentration of oestrogen and progesterone receptors compared with those in ovariectomized controls. However, the sequential treatment of ovariectomized animals with prolactin + progesterone stimulated uteroglobin production to a concentration equal to that found in intact rabbits on the 5th day of pregnancy. This was not achieved by prolactin or progesterone alone or with oestradiol. These results suggest that prolactin acts as an essential factor in the rabbit uterine response to progesterone, perhaps by the modulation of progesterone receptor activity.     

Production and characterization of an antiserum to synthetic gonadotropin-releasing hormone

The synthetic decapeptide “luteinizing hormone-releasing hormone” (LH-RH) was rendered antigenic by reaction of its histidine or tyrosine residues (7 : 3 approx.) with p-diazonium phenylacetic acid and coupling of the azo-derivatives formed to bovine serum albumin (BSA). Immunization of rabbits yielded antisera that bound ¹²⁵I-labeled LH-RH (approx. 50 pg) at dilutions up to 1:200, 000 and showed no cross-reaction with unrelated hypothalamic and pituitary hormones, extracts from rat cerebral cortex, and with small fragments of LH-RH. Cross-reaction was minimal (0.2%) with the free acid analogue of LH-RH, and moderate with $\text{des}$-pGlu LH-RH (20%), $\text{des}$-pGlu-His-LH-RH (2.4%) and with LH-RH analogues in which a single residue (No. 4–6 or No. 8) was exchanged by an amino-acid of similar character (1.2–12%). Biologically active hypothalamic extract and LH-RH produced parallel ¹²⁵I-LH-RH-binding inhibition curves, providing immunochemical support for the identity of the native releasing hormone with synthetic LH-RH.